We present a comprehensive review of how to best use neuro-toxins and fillers to rejuvenate the aging face. With modern neuro-toxins and fillers, it is now possible to achieve an improvement in the aging changes of young, middle-aged, and older patients. Furthermore, with the appropriate application of these materials, surgical results can be kept looking good without the need for repeated surgical intervention. As it is important to understand the relationship of the different parts of the face when assessing the aging face, we review the best practices as applied to the whole face.

After delivering a recent course on rejuvenation of the face at a plastic surgery meeting in India, I was approached by no fewer than twenty physicians, seeking advice on how to improve perceived imperfections on their own faces. It was revealing that every one of these physicians seeking advice was under the age of 50 years, and most were in their 30s. I have had similar requests after lectures in Singapore, Australia, the Middle East, and Europe. Such is the desire to maintain a youthful appearance in all parts of the world!

Once facial aging has been properly understood, options of management present themselves in a logical manner.[1],[2] Whereas surgical intervention still continues to give the most profound improvement, advances in neurotoxins, which work by denervation, and facial fillers now allow the modern cosmetic surgeon to have a palette of options to present to the patient.[3],[4],[5] Neurotoxins relax injected facial muscles, reducing both dynamic as well as static wrinkles: the aim is to carefully use the chemical to modify the balance of muscular actions in the face. For the purpose of this article, all units will refer to botulinum toxin A (BTA Botox, Allergan, Inc., Irvine, California), but other neurotoxins may be used in a similar fashion. We use a concentrated solution with one cubic centimeter of solution containing 100 units of BTA. Fillers provide space-filling volume for varying periods, depending on the makeup of the specific filler.[6]

As the method of action of neurotoxins and the basic makeup of different fillers have been covered in detail in many articles, we will concentrate on giving the cosmetic surgeon various tips on how to get the best results by using these agents, usually in combination. It will be assumed that the reader is familiar with the different neurotoxins and filling agents.[7],[8],[9] We will discuss broad categories of fillers, rather than discussing each individual filler available in the market, especially since brand names will differ from country to country. Space-filling fillers discussed will include basic hyaluronic acid (HA) fillers (Restylane, Juvederm) which last about 6 months, denser products (Juvederm Ultra Plus, Perlane), which persist for 9–12 mont''s, and biostimulatory fillers which induce neocollagenesis (Radiesse and Sculptra). There are many other fillers available which fall broadly into these two groups. We do not use any so-called permanent fillers to avoid permanent problems.

HA agents are naturally occurring molecules which are degraded by the body. Radiesse ® is calcium hydrozyapatite microspheres which are similar in composition to the mineral in human bone and teeth: they are suspended in an aqueous carrier gel. It has been found that, as these microspheres induce local histiocytic and fibroblastic responses, new collagen around the microspheres is formed. This has been borne out in clinical practice as some residual effect of the injections seems to remain.

Sculptra is poly-l-lactic acid (PLLA): it is a biocompatible, biodegradable, synthetic polymer derived from the alpha-hydroxy acid family. A subclinical inflammatory response is followed by encapsulation of the microsphere and subsequent fibroplasia.

Clinical Uses of Neurotoxins and Fillers: Tips, Tricks, and Suggestions

It is assumed that the surgeon has analyzed the patient's face with the help of a mirror and/or photographs and has considered all options, including neurotoxins, fillers, and surgical procedures. Many of our patients will present looking for advice on how they may improve certain or all aspects of the face. Although some will specifically present with a request for a particular procedure, many will seek an analysis and advice. With the help of photographs and sketches [Figure 1] and [Figure 2], we go over the pros and cons of various treatment modalities. We will not cover surgical options in this discussion.

[Figure 1] shows all the sites where BTA may be of help. We will present our experience with each of these sites and submit some subtleties of treatment. Fillers often go hand in hand with neurotoxins and therefore, it is impossible to discuss one without the other. Therefore, [Figure 2] shows all the sites where fillers may be of help. Please refer to these two figures as we discuss the combination treatments at some or all of these sites

Frown lines and frown muscles

The most common use of neurotoxins is in this area. Many texts give a formula of a number of units to be injected at three sites in each brow. We find this formulaic approach less useful. We generally ask the patient to face us with the muscles relaxed and assess the depth of the vertical and horizontal glabellar lines and then assess the depth with frowning. Furthermore, we put an index finger over where we think the lateral courrugator muscle is along the upper border of the brow and ask the patient to frown. One is always surprised at the variability of the length of the corrugator muscle. We also do not feel that injecting on either side of a furrow serves much purpose. Rather, we inject between 20 and 40 units of the BTA into the corrugator and procerus muscles. We spread our injections over as many as 8–12 injection points and give it deeper into the muscle, rather than subdermally, as has been advocated. We inject quite low into the procerus muscle to convert the collapsed “fat nose” into a “slim nose.”

When the tail of the brow needs to be lifted,[10] we inject a total of 4 units at two points, again examining the maximal force of the orbital orbicularis. So, we dynamically assess each patient and tailor the injections accordingly. We also draw and indicate the dose and site of the BTA so that subsequent adjustments may be made depending on the response. As these nonsurgical treatments are certainly not cheap, we review every new patient after a month to ensure whether the desired effect has been achieved and make any adjustments if necessary.

The aim of the injections is to reduce the dynamic as well as the static frown lines, elevate the tail of the brow, and smooth out the glabellar area. Patients with deep static furrows may need filler. We usually allow our patients to see how much of an improvement the BTA alone achieves so that they may help us decide if a filler is indicated. If a filler is indicated, we use Restylane ® exclusively and inject in very small dosages with massage of the material into the groove. We do not inject deeply and have recently converted to injecting in this area with a blunt cannula to avoid intravascular injection. We found that HA fillers in this area last more than a year. Usually, no more than half a vial of filler is needed in this area [Figure 3].

Figure 3: Thirty units of botulinum toxin A and half a vial of Restylane® give a nice improvement in the static and dynamic frown lines and a pleasing lift to the tail of the brow

There have been numerous articles that recommend removal of brow fat during eyelid and brow surgery: this is a grave error.[11] Aging results in loss of brow fat with resultant lack of the youthful fullness. Whereas we regularly inject fat into the brows when performing facelifts or other surgical facial esthetic procedures, injection with HA also gives an excellent result. Although brows will swallow one vial of filler in each brow with ease, we generally inject half a vial in each brow, aiming to get a satisfactory improvement. The aim is to inject deeply into the brow fat pad itself and above the superior orbital rim so that it raises the brow and gives a pleasing smooth curve to the sub-brow area. Poorly addressed brows are not uncommonly seen after surgery or after BTA and filler injections: the mantra should be to aim for smoothness and achieve a good position and a pleasing shape.

Forehead

When patients have marked horizontal static and dynamic lines on the forehead, it is important to not neutralize the frontalis muscle completely: this invariably results in brow ptosis. We have found a safe way of improving forehead lines without dropping brows: we perform micro-droplet BTA injections subdermally at many points on the forehead.[12] No >1–2 units of dilute BTA are injected at many points on the forehead but never lower than 1 cm above the brow: this leaves the lower frontalis muscle active and has been successful in preventing brow ptosis. The aim is to improve but not eradicate the forehead lines. We will inject between 10 and 15 units of BTA across the forehead [Figure 4].

Figure 4: Thirty units of botulinum toxin A to the frown muscles and to lift the tail of the brow, ten units of micro-botulinum toxin A treatment across the forehead lines, 1.5 vials of Radiesse® on each lower face (nasolabial, mandibulolabial, and prejowl sulcus) take away the worries and aged look very nicely. Note the improvement in the jawline with the prejowl injection

Some surgeons have suggested injecting HA across the forehead to “thicken” the forehead. We found that this leaves irregularities requiring frequent use of hyaluronidase and therefore do not inject the forehead with fillers. Furthermore, for the improvement seen, one requires several vials of HA, making it an expensive treatment with minimal advantage. A good regular moisturizer used after judiciously performed BTA injections gives very pleasing results.

Temple hollows

We have seen overaggressive filling of the temple hollows. The aim of injecting the temple hollows is to restore the natural smooth arc of youth from the hairline, over the zygomatic arch, leading to the malar eminence.[13] A slight undercorrection is perfectly reasonable as an overfilled temple is most unbecoming.

Sculptra ® or Radiesse ® may be used: we inject Radiesse ® deep into the superficial temporalis fascia in little boluses and massage the material into the space. Many older patients will have prominent veins, so we inject with operating loupes and with good illumination. The aim is to blunt the ridge at the temporal fusion line and also create a smooth transition onto the zygomatic arch. Most patients who need to have a filler injected will need one vial of Radiesse ® per side because of the area. However, we frequently inject half a vial per side and use most of it to feather the edges of the hollow, thereby giving a relatively smooth curve. Bruising is very common: we apply ice during the procedure and ensure patients use ice for the next 24 h.

Deep upper eyelid sulci

Deep superior sulci may be age related or, more commonly, may be the result of aggressive fat removal at blepharoplasty. These deep hollows are not only unsightly as they expose the bony orbital rim and give the patient a gaunt appearance, but they also result in lagophthalmos as the skin and orbicularis muscle adhere to the levator aponeurosis, with resultant posterior pull of the upper eyelid skin and muscle.[14] HA fillers are useful to improve both these problems. The injections are administered deep, close to the periosteum and the hollow is filled from the orbital rim and roof forward. Again, we use an inject and massage technique and always bring the patient back 3 weeks later to finish the injections as it is impossible to obtain a smooth correction with one injection every time. Fillers in this area, like in the glabella and the lower eyelid hollows, last more than a year, often two. Separation of the adherent skin and orbicularis muscle allows a better dynamic to the upper eyelid, allowing better closure [Figure 5].

Figure 5: Excessive removal of fat and skin from the upper eyelid results in skeletonization of the superior orbital rim and lagophthalmos. One vial of Restylane® was injected against the orbital rim and orbital roof, and some deep into the orbicularis into the sulcus to soften the harsh look and improve eyelid closure

Crow's feet lines tend to be static as well as dynamic. With age, these lines, which radiate outward, will spread lower down onto the lateral cheek and become static. In patients who have had overly aggressive lower eyelid blepharoplasty, it is not uncommon to see the lines spread across the lower eyelids medially. We take a three-pronged approach to extensive crow's feet: two to three units of BTA per site are first injected as shown in [Figure 1] around the orbital rim at three or four points. We then inject micro-droplet BTA with one unit per site with the dilute BTA at numerous sites where the lines are present. Injection into the origin of the zygomaticus major muscle is avoided by injecting almost intradermally. About a quarter of a vial of HA is injected subcutaneously in very small boluses and massaged into position. In patients willing to undergo the treatment, the third part of the treatment is fractionated CO2 laser to the lower eyelids and smile lines. Once again, it is important to explain to the patient that a genuine smile, also termed a Duchenne smile, involves movement of the muscles around the eyes. Smiling with the peri-oral muscles alone makes one look “false.”[15]

If the lower eyelid is riding too high, as is sometimes seen after tran-conjunctival blepharoplasty, or in the presence of a dynamically active pretarsal orbicularis oculi muscle, injecting about one to two units of BTA into the pretarsal orbicularis can give a nice improvement in the lid position without causing an ectropion.

Bunny lines

Lines lateral to the nasal bridge are often neglected and result in oblique wrinkles, caused by overactivity of the procerus and the depressor supercilii muscles. They respond very well to about 4–6 units of BTA per side.

Nasojugal groove and malar groove

As the cheek fat pad descends, the orbitomalar ligament lengthens and the inferior orbital rim is exposed with hollows medially (tear trough) and laterally (malar groove or “Charlie Brown” line): these hollows can be improved significantly with HA fillers. An understanding of the periorbital anatomy is vital.[16] We usually begin with about half a vial per side and increase the volume about a month later as indicated. It is common to get a slightly lumpy appearance for the first few weeks. Injections must be given deep to the orbicularis muscle and either a threading or bolus injection method may be used. We generally inject a small bolus and massage it (mold it) into position. It is important to inject just below the groove and massage it into position. If the bolus is injected directly into the groove, “lumpiness” is likely to result. It is very much an art form: irregularities, edema, and overfilling are commonly seen and may require the use of hyaluronidase to dissolve some of the fillers. The Tyndall effect (a slight bluish hue under the skin) is an optical phenomenon seen when HA is injected superficially. Properly done, these result in very gratifying results, often lasting 2 years or more [Figure 6].

Figure 6: Two and a half years after injection of the malar crescent with half of a vial of Restylane® on each side

A number of materials are used when augmenting the malar eminence: Sculptra ®, Voluma ®, Restylane ®, Juvederm ®, Perlane ®, Radiesse ®, etc. The injector should become familiar with one or two of these materials to get a reliable and predictable result. Biostimulatory fillers such as Sculptra ® will expand; therefore, undercorrection should be the aim. This is less of a problem with Radiesse ®. Since we can mold Radiesse ® into the required shape and position, we inject Radiesse ® preperiostially and massage it into position. One vial (1.5 ml) per side is not unusual and some patients may need more. Again, it is always wiser to underfill and build it up gradually.

It is important to remember that malar filling is not just about filling the “egg-shaped” fullness that models have over the zygoma. With aging, there is loss of the deep malar fat pad which is medial to the infraorbital nerve. In the deep malar fat pad, we usually use HA, as one does with the nasojugal groove. When the malar eminence is properly augmented, it will show off the submalar hollow, which is a gentle curve from the zygomatic arch, over the egg-shaped malar fullness with a gentle submalar hollow [Figure 7]. A properly augmented midface will also give a softening nasolabial fold. Always aim for undercorrection in men as it is easy to effeminize them.

Figure 7: This patient received Restylane® injections into the malar crescent, followed by Radiesse® injections into the nasolabial folds and a small amount (half a vial per side) into the malar region. These are the types of faces seen in the Mediterranean and Indian peoples and respond very well to judicious injection with fillers

The fullness just above the nasolabial fold and the mandibulolabial fold is caused by a combination of descent of the malar fat pad, atrophy of deeper tissues in the midface, and perhaps some excess of fat in this region. Direct excision is never a good idea as even the best of scars is suboptimal. In combination with malar filling, these two grooves are filled in a fan-shaped manner when close to the nose (the groove widens as it nears the nose). It is important to mold the filler by injecting (either a bolus or threading technique will do) and massaging it externally as well as with a finger inside the mouth. One must never aim for complete effacement [Figure 4] and [Figure 7]. In patients with deep grooves, each side can easily gobble up one to two vials of Radiesse ®. Due to the active use of the perioral region, most of these fillers will last up to 9 months, but rarely longer.

Platysma bands

In patients with prominent platysmal bands, dividing about 10–15 units per band of BXA gives reasonable results [Figure 8]. However, it does not efface them completely, and the duration of action is only about 2 months. For more complete effacement, one has to use as much as 60 units in the various platysmal folds. It does not improve horizontal rhytids in the neck.

Figure 8: Twenty units of botulinum toxin A per platysmal band giving a reasonable relaxation of the bands

Vertical perioral rhytids, also called smokers' lines, are usually static lines which are exacerbated with pursing of the lips. Although physicians do inject small quantities of BTA in the four quadrants of the lips, any significant effect would also result in an effect on the use of the lips. Therefore, we do not advocate the use of BTA for lip lines. Instead, we treat them with fillers and an ablative laser.

As far as fillers are concerned, there continues to be a tendency to give patients hemorrhoid lips, with overly aggressive fillers into the upper and lower lips. We usually use fillers conservatively to improve the vermillion border, the white roll, and give some fullness to the central lower lip and a more moderate filling to the upper lip. Always start with only one vial of HA. It is important to study the surface anatomy of beautiful lips to appreciate the best method of augmenting lips. We also attempt to create the philtral columns when we inject in the perioral region as this gives lips a youthful look [Figure 9]. As injecting lips can be very uncomfortable, we usually give a “dental” block. Always undercorrect when it comes to lips! With vertical lip lines, one attempts to give the bases of the grooves some support without overfilling the upper lip. Finally, never augment the lips all the way to the angle of the lips (cheilion).

Figure 9: Accentuating the philtral columns and recreating the ridge at the white roll of the lip give lips; structure. Note the improvement in the fine lines. Also, little or no filler is injected into the lateral-most section of the lips

The mentalis muscle sometimes shows quivering movements as we age (pebble or golf ball chin). Although this is frequently seen with aberrant nerve regeneration following facial nerve palsy, one also sees it in others. A small amount of Botox ® (2–4 units per side) usually controls this nicely.

During facelifts, we used chin implants frequently. Nowadays, we only use them when there is profoundly deficient chin projection. In others, we either use fat grafts or fillers like Radiesse ®. Half a vial of Radiesse ® injected deep against the bone will give a nice improvement in chin projection.

Depressor anguli oris, jowls, and jawline

The downturned angle of the mouth may be improved by injecting 4–5 units of BTA in each depressor anguli oris. This is a fan-shaped muscle that originates from the oblique line of the mandible and inserts into the modiolus. The anatomy of this muscle is frequently drawn inaccurately: [17] it fans from the modiolus downward and outward. A guide that has always worked for me is to place a finger vertically at the angle of the mouth and inject just lateral to the finger. However, depending on racial characteristics, it may be important to review the anatomy of your local population.

The prejowl sulcus which accentuates the jowl can be filled with Radiesse ® to create a straighter jawline. It is a powerful injection if placed deep against the periosteum and massaged into place. Local edema may occur and the filler may be palpable for the first few days. Aim for a slight undercorrection. Radiesse ® may also similarly be used to correct irregularities of the mandibular border and to also accentuate the mandibular angle. Several vials may be needed for this and cost becomes an issue.

In women with prominent masseter muscles, slimming of the face may be achieved with about 20 units of BTA divided into each masseter muscle. The results can be very gratifying and may last as long as 6 months [Figure 10].

Irregularities, especially of the nasal dorsum, can be camouflaged with judicious application of fillers. A nasal hump may be hidden and a depressed area can be filled. This technique is popular in Asia where flat nasal bridges are brought forward with fillers.

Whereas judicious use of neurotoxins and fillers can give very impressive results, a word of warning is warranted: there has been much made about “liquid facelifts” in the media and advertisements. When a “total liquid facelift” is attempted, one can never quite get the result of a well-done facelift, and the total cost of neurotoxins and fillers comes to 10,000–15,000 dollars! Only to be repeated every 6 or so months! It beggars belief that these procedures are promoted and performed. Go gently into the night is our motto. And, there is no substitute for subtlety.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

This study was supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, NY, to the Department of Ophthalmology and Visual Sciences, University of Utah.